This invention relates to a new class of thienamycins (I) and their pharmaceutically acceptable salts and esters which are useful as antibiotics: ##STR3## wherein the stylized radical (hereafter referred to as R'): ##STR4## attached to the amino nitrogen group of thienamycin represents a mono- or polycyclic N-containing heterocyclic group; R is, inter alia, hydrogen, substituted and unsubstituted: alkyl, aryl, alkenyl, heterocyclylalkenyl, aralkenyl, heterocyclylalkyl, aralkyl, --NR.sub.2, COOR, CONR.sub.2, --OR, or CN. The heterocyclic radical R', is further defined below.
Thienamycin and all of its isomers are known and are described by structure 1, below. In this regard, reference is made to U.S. Pat. No. 3,950,357 issued Apr. 13, 1976 which is directed to thienamycin and to co-pending, commonly assigned U.S. patent application Ser. No. 17,680 filed Mar. 5, 1979 which is directed to the total synthesis of thienamycin and all of its isomers. To the extent that the cited patent and application provides starting materials for the practice of the present invention, they are incorporated herein by reference. ##STR5##
The compounds of the present invention are most conveniently isolated as the zwitterionic species demonstrated by structure I.
This invention also relates to processes for the preparation of such compounds (I); pharmaceutical compositions comprising such compounds; and to methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.
There is a continuing need for new antibiotics. For unfortunately, there is no static effectiveness of any given antibiotic because continued wide scale usage selectively gives rise to resistant strains of pathogens. In addition, the known antibiotics suffer from the disadvantage of being effective only against certain types of microorganisms. Accordingly, the search for new antibiotics continues.
Thus, it is an object of the present invention to provide a novel class of antibiotics which are useful in animal and human therapy and in inanimate systems. These antibiotics are active against a broad range of pathogens which representatively include both gram positive bacteria such as S. aureus, Strep. pyogenes, and B. subtilis, and gram negative bacteria such as E. coli, Pseudomonas, Proteus morganii, Serratia, and Klebsiella. Further objects of this invention are to provide chemical processes for the preparation of such antibiotics and their non-toxic pharmaceutically acceptable salts and esters; pharmaceutical compositions comprising such antibiotics; and to provide methods of treatment comprising administering such antibiotics and compositions when an antibiotic effect is indicated.